Treatment options

INTRACYTOPLASMIC MORPHOLOGICALLY SELECTED SPERM INJECTION (IMSI)

What is IMSI?

• IMSI is an advanced laboratory technique used to select sperms for fertilisation.it is a real time method where sperms are selected under very high magnification ( around 6000 times) which is much higher than the standard 400 times magnification high is used in ICSI,.

• With this magnification the morphology of sperms can be better seen so selecting the sperms with better morphology can improve the embryo quality and decrease the likelihood of failure and the likelihood of miscarriage.

What are the advantages of IMSI?

This technique is found to be useful in cases with recurrent IVF failure and in patients with poor morphology of sperms.

CRYOPRESERVATION

Cryopreservation or freezing is a technique, in which the body cells/ tissue are frozen in ice for use at a later date. The frozen specimen is recovered intact when its time to use the by a process called thawing. This technique is now used quite commonly in fertility management and can be used to freeze eggs, sperms or embryos depending on the requirement. Freezing technology has evolved over time and the pregnancy rates using frozen sperms/ eggs/ embryos are as good as with fresh ones.

Embryo Cryopreservation

The technique of cryopreservation has evolved over time, with vitrification being a major breakthrough in this field. The term vitrification is derived from a Latin word “vitrium”, which means “glass”. The process of vitrification involves cooling the embryos rapidly, which turns the cellular content into a glass like substance without allowing any time for formation of ice crystals. Ice formation risks the cell rupture because water expands when it forms ice. The embryos are than dipped in liquid nitrogen and stored in at ¬–196 degree centigrade. This brings all cellular activity to a halt and allows the embryos to remain viable for indefinite period of time. The recovery rate on thawing the vitrified embryos is excellent. Therefore, embryo cryopreservation has now become an excellent tool for freezing the embryos. Embryos can be frozen at any stage of development from day 1 to day 5. We prefer to allow the embryos to grow for some time before freezing, so that the quality of embryos formed using IVF/ ICSI can be assessed and we freeze only the good quality embryos with high potential of producing pregnancy on being transferred.

The most common indications for embryo freezing include

1. Extra good quality embryos formed after IVF/ ICSI- These frozen embryos can be used later in case the initial transfer fails or the couple decides to try for another child after a first successful embryo transfer.

2. Embryo freezing allows for transfer of lesser (more justified) number of embryos, thus reducing the risks of multiple pregnancies.

3. Embryo freezing reduces the complications rates in patients who are hyper stimulating, as embryo transfer can be deferred to a later (cold) cycle. This happens as the physiological status of the hyper stimulating woman is more settled in a later cold cycle.

4. Embryo freezing offers an option to couples desirous to having a child later, but are at risk of losing their fertility because of some surgery or gonadotoxic treatment like radiotherapy of chemotherapy.

Egg cryopreservation

Eggs can be frozen using the same technique of “vitrification”, as described above for embryo freezing. The most common indications for cryopreservation of eggs include:

1. Women with advanced age, but still waiting for a right partner, can get their eggs cryopreserved for use in future.

2. For fertility preservation in fertile women undergoing any treatment that can suppress or reduce their fertility after the treatment- such as chemotherapy, pelvic radiation, surgery.

3. Sometimes eggs retrieved from donors can be cryopreserved to build an oocyte bank.

Sperm Cryopreservation

Sperm freezing is a rather simpler and well defined procedure and has been in use for decades. Sperms stand the freezing process very well and can be thawed easily.The common indications for sperm freezing include:

1. As a backup in cases where the male partner may not be available on the day of IUI/ IVF to provide fresh semen sample

2. When there is apprehension of the male partner not being able to produce a semen sample on the day it is needed.

3. Before the male partner is to undergo treatments like chemotherapy, which will likely affect his sperm count adversely and even make him azoospermic.

4. In men with oligospermia where multiple semen samples may be frozen to accumulate sperms.

5. In azoospermic males where the sperms have been recovered surgically using techniques like MESA, PESA, TESA. Sperms can be frozen in multiple aliquot to help the patient avoid having to have the surgery again.

BLASTOCYST CULTURE AND TRANSFER

What is a blastocyst?

Embryos can be cultured in the lab for up to 5-6 days, when provided with good nutrition in terms of media and environment. Such cultured and grown up embryos are called as blastocysts. Since the blastocysts have made it through the key growth process, they offer a greater chance of successful implantation and pregnancy.

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What are the advantages of blastocyst transfer?

One of the biggest challenges in IVF is the ability to select and transfer an embryo with the best implantation potential and highest probability of resulting in a pregnancy. The traditional practice to achieve a higher probability of implantation and pregnancy has been to transfer more than one embryo in the uterus on the 2nd or 3rd day of development. Blastocyst culture is a better alternative to achieve the same objective, as it allows us to grow the embryos in laboratory for a few extra days, after which the best quality grown up embryo (called as a blastocyst) can be transferred into the uterus. Such selection enhances the chances of implantation and improves the chances of achieving pregnancy without putting the woman at risk of multiple pregnancies and its complications such as prematurity, IUGR and foetal loss.

However, blastocyst culture is a not a suitable technique for all patients. This technique is not so useful especially in cases where a fewer number of eggs are retrieved or a fewer no of embryos are formed. In such cases, additional embryo culture in laboratory will not improve the pregnancy rate. Therefore we always discuss this option with our patients in conjunction with our embryologist in order to evaluate the pros and cons of blastocyst culture for a particular case/ situation and then individualize the decision to each case.

ASSISTED HATCHING

Assisted hatching is a laboratory procedure performed on the embryo before the embryo transfer. In this technique a very small hole is made in the outer shell of the embryo (called as the zona pellucida), before placing it in the uterus. As part of normal process of implantation, the embryo has to hatch out from the zona pellucida in order to implant in the uterus. Therefore, making a hole in the zona pellucida of the embryo before placing it in the uterus assists the embryo in coming out of this shell and facilitates implantation.

What are the techniques of assisted hatching?

There are two methods of performing assisted hatching-

1. Mechanical/ Acid digestion hatching– The procedure is done under microscope using a micro needle.

2. Laser assisted hatching– Laser hatching is the latest and a more accurate technique of assisted hatching, in which a beam of laser is directed to the embryo to make a hole on the embryo. It involves minimal mechanical handling of the embryo, is quick to perform and is a very accurate method to deliver a hole in the embryo.

What are the benefits of assisted hatching?

Assisted hatching benefits the following sets of patients-

1. Women with recurrent implantation failure

2. Women undergoing frozen embryo transfer– Freezing tends to harden the zona pellucida of the embryo, which may be a little more difficult for the embryo to breach. Thus, frozen embryo benefits from assisted hatching as it increases the chances of successful implantation.

3. Women elder than 37 years of age, who are undergoing IVF

4. Thick Zona- Zona pellucida >40 microns thick.

EGG DONATION

Egg Donation is a treatment option for women who cannot conceive with their own eggs. The eggs donated by younger women are fertilised with the patient’s partner’s sperm and transferred in an appropriately prepared womb of the recipient. The patients or candidates for egg donation are women with

1. Premature Ovarian failure
2. Menopause
3. Iatrogenic ovarian failure due to surgery or radiation
4. Resistant ovary syndrome
5. Carriers of recessive autosomal disorders
6. Poor ovarian reserve
7. Women > 42 yrs as chance of becoming pregnant with own egg are very less.
8. Poor egg quality or multiple failed IVF attempts.

Steps in Egg Donation: The important steps in the egg donation program include

Egg donor screening and selection

The egg donors are selected from a pool of egg donors available with the egg donor agency. They are generally in the age of 21-31 yrs with preferably having at least a child and as stipulated by the draft guidelines of ICMR the procedure is a confidential and anonymous process. The identity of the donor and recipient is kept confidential and not revealed to each other at any point of treatment or later. However, we make every effort to select and match the donor profile according to the recipient.

The process involves a comprehensive physical and psychological evaluation of the donors, as it is important that they understand the whole treatment and also understand that they will have no right on the child conceived through their eggs.

A detailed medical history is obtained and the patient is tested for infections, ultrasound evaluation is done for evaluation of ovarian reserve and hormonal status of the donor is also tested.

Synchronisation of Donor’s and recipient Cycle

The next step is the synchronisation of the cycle so as to simultaneously prepare the uterus of the recipient for the embryo transfer along with the donor’s egg. This is done by first programming the cycle of both women using birth control pills which is given for 2- 3 weeks and stopped simultaneously so that they start menstruating around the same time.

Ovarian stimulation of donor and endometrial preparation

The donor undergoes stimulation (as mentioned above) and recipient’s uterine lining is prepared using Oestradiol tablets to achieve an optimal lining of 8 mm or more.

Egg retrieval and fertilisation

The egg retrieval and fertilisation steps remain the same as in standard IVF cycle, and on the same day of egg retrieval we start progesterone (either vaginal tablets or daily injections ) to induce the final changes in the lining of the recipient and prepare it for implantation, the embryos are transferred back in the recipient’s uterus. The pregnancy test is due 2 weeks after the embryo transfer. This is one of the most successful ART treatments with up to 60% success rates and 40-45% pregnancy rates.

EMBRYO ADOPTION

What are the indications for Embryo adoption?

Embryo adoption is a good option for infertile couples having both male and female factors, who are unable to produce enough good quality eggs and sperms. Although it can be debated whether these patients will benefit more by adopting a child or an embryo, we give our patients both these options and discuss the pros and cons of both the options. This helps them make a well informed decision on how to realise their dream to have a child. Many a times, couples having suffered from long term infertility prefer to adopt an embryo, as it gives them the opportunity to go through the process of pregnancy and child birth. Embryo adoption also allows the adopting couple to avoid social stigma of adoption by keeping the whole process discrete and to screen certain physical characteristics of the donating parents.

Where can the patients adopt embryos from?

Many patients who get a successful outcome from IVF and have spare frozen embryos often decide to donate their frozen embryos either for research or for other childless couples. We discuss the opportunity for donation of extra frozen embryos with all our patients who complete their family with IVF and are left with spare frozen embryos. Such couples who have themselves gone through the process of assisted reproduction to realise their dream of having a child are generally very sympathetic towards such requests and feel happy about the prospect of giving the joy of parenthood to other couples in need of embryos.

SURROGACY

Surrogacy is an arrangement when another woman carries and gives birth to a baby for the couple who want to have a child. It is a means of third party reproduction in which the surrogate is only a “gestational carrier”, a gestational carrier is woman who accepts to bear (or be pregnant with) the child of another woman who is incapable of becoming pregnant using her own uterus. The gestational carrier provides a host uterus for the offspring, and does not contribute genetic material, i.e. is not the egg provider. The offspring’s genetic material may come from the egg and the sperm provided solely by the aspiring man, woman or couple, referred to as the “intended parents,” or in combination with donor egg and/or donor sperm, depending on the needs of the intended parents.

It is an accepted treatment option for couples and recognized by the government of India. The various reasons for doing surrogacy include those women who:

1. Do not have a uterus like in congenital absence of uterus or post hysterectomy.
2. Have an abnormal uterine cavity
3. Have had several recurrent miscarriages
4. Have had recurrent failed IVF cycles
5. Have a medical reason for which pregnancy is inadvisable

At blessings fertility we adhere to the guidelines laid by the government of India and always refer our patients to the surrogate agency / ART bank to help find an appropriate surrogate. Once the appropriate surrogate is finalized we synchronize their cycles and take care of every step in the treatment till the embryo transfer is done.
Surrogacy services at Blessings Fertility Center are provided as per the provisions of the Govt. regulations under the ART services bill if India. In short, this bill provides for the following rules to govern surrogacy practice in India:

1. Surrogacy by ART should be considered only for patients for whom it is physically or medically impossible / undesirable to carry a child to term.

2. Individuals or couples may obtain the service of a surrogate through an ART bank.

3. The person or persons who have availed of the services of a surrogate mother shall be legally bound to accept the custody of the child / children irrespective of any abnormality that the child / children may have, and the refusal to do so shall constitute an offense.

4. A couple or an individual shall not have the service of more than one surrogate at any given time.

5. A couple shall not have the simultaneous transfer of embryos in her and the surrogate.

SURGICAL SPERM COLLECTION METHODS

Sperm are produced inside the testes and they mature and become motile, as they travel through the epididymis. During ejaculation, the mature sperms are carried from the epididymis to the penis along the vas deferens. Normally this ejaculated sperm is used for fertilisation, however in a subgroup of infertile male there is no sperm present in the ejaculate leading to azoospermia. Any anatomical, infectious, traumatic or developmental anomaly like congenital absence of vas deferens in this passage for sperms can lead to obstructive oligospermia/ azoospermia (~40% of all cases of azoospermia). On the other hand, non-obstructive azoospermia can result from absence or very poor sperm production inside testes (~60% cases of azoospermia) and can result from hormonal abnormalities, varicocele or testicular failure.Until very recently there was no effective treatment for men suffering from azoospermia. In obstructive azoospermia the reason for the absence of sperm in the ejaculate is physical and in general, does not involve the process of sperm production. Therefore in most cases surgically retrieved sperm are normal in their function and fertilization rates and pregnancy rates are similar to those obtained using ICSI on ejaculated sperm. Men with congenital absence of vas should be investigated for genetic diseases like cystic fibrosis.

There are three methods of surgically retrieving sperm from the testis

1. Percutaneous Epididymal Sperm Aspiration (PESA)

PESA is a simple technique to obtain sperms for Intra Cytoplasmic Sperm Injection (ICSI) in men with infertility due to obstructive azoospermia. PESA is generally carried out under local anaesthesia and in most of the cases it’s performed only on one side, but sometimes it becomes necessary to do this simultaneously on both the testes.
After taking informed consent from the couple, giving local anaesthesia and cleaning scrotum with antiseptic solution, the doctor locates the vas deferens and then inserts a fine needle into the vas deferens, while an assistant pulls back the plunger to aspirate seminal fluid. The embryologist examines the seminal fluid to locate motile sperms in the sample. The procedure may need to be attempted again until motile sperm have been found. After the procedure the man will be asked to wear a very tight pair of underpants to provide support to the scrotum and avoid pain and swelling of scrotum.

The procedure is usually performed just prior to the ovum retrieval in the female partner. In case, no sperms are found in the aspirate, egg retrieval may be cancelled or donor sperms used for fertilization.

2. Testicular Sperm Extraction (TESE)/ Trans Epididymal Sperm Aspiration (TESA)

This procedure involves giving a small incision over the testes and taking out a small piece of seminiferous tubule tissue to isolate sperms from the tissue sample. This procedure is used for sperm extraction in patients with severe obstructive oligospermia. It can also be used to find some live and motile sperms in patients with non-obstructive azoospermia, in which there may still be some small areas of sperm production in otherwise non-functional testes. The number of viable sperms isolated is generally smaller than with PESA and the sperms are generally not fit for freezing. As with PESA, TESA is also performed just prior to the egg retrieval so that ICSI can be performed simultaneously. In cases, where even TESA/ TESE doesn’t yield live and mobile sperm, egg retrieval can either be cancelled or the retrieved eggs can be frozen.

In some cases, the procedure yields only immature sperms. These immature sperms cannot be used for ICSI because the fertilization rates with immature sperm are very poor and even if fertilization does occur, there is high possibility of miscarriage following transfer of such embryos. Not only this, use of such immature sperms can lead to serious chromosomal disorders in the offspring.

3. Microdissection TESE

This is one of the most advanced techniques of sperm extraction in men with non-obstructive azoospermia that is in men having problem with sperm production. Microdissection TESE is performed in the operating room and under general anaesthesia using an operating microscope. It is based on the principle that in azoospermic men there may be some islands of spermatogenic activity, which are not identifiable with naked eyes but can be identified using a microscope and can be dissected away. The tubules in such islands of normal tissue appear healthier, dilated and more opaque in comparison to adjoining abnormal tubules. Using the magnification of the operating microscope, the surgeon picks only the healthy looking seminiferous tubules thus optimising the chances of sperm retrieval. This process can help in retrieving sperms in men with previously failed testicular biopsies and also reduces the amount of testicular tissue removed during the procedure. The extra sperms retrieved by Microdissection TESE are cryopreserved for future IVF/ICSI also.

Microdissection TESE is carefully coordinated with the female partner’s egg retrieval, and is performed either the day before egg retrieval or on the same day. This allows each partner to be there for the other’s procedure.